BAPS prize lecture: New insight into mechanisms of parenteral nutrition-associated cholestasis: role of plant sterols. British Association of Paediatric Surgeons.
OBJECTIVE
Infants on long-term parenteral nutrition frequently will have progressive cholestatic liver disease, the cause of which remains largely unknown. The aim of this study is to establish a possible role for plant sterols (phytosterols) in the pathogenesis of parenteral nutrition-associated cholestasis (PNAC).


METHODS
Two experimental studies were used: (1) A study on neonatal piglets involved the daily injection of plant sterols; measurement of their concentrations in serum, liver, and bile during a 14-day period; and determination of serum bile acid concentrations, bile acid secretion, and bile flow at the end of the 14-day period. (2) Isolated rat hepatocyte couplets were used to study the effects of sterols on canalicular secretion.


RESULTS
The daily injection of phytosterols (in amounts similar to those given to infants who receive parenteral nutrition) led to their progressive accumulation in the piglets' serum, liver, and bile. Serum bile acid levels were significantly higher in the sterol-treated piglets. Maximal bile acid excretion was significantly lower in the sterol group. Phytosterols caused a significant inhibition of secretory function in isolated rat hepatocyte couplets.


CONCLUSIONS
Important contaminants of commercial lipid emulsions (phytosterols) have been identified as a possible cause of PNAC.
Iyer
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Spitz
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Clayton
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D000818:Animals; D000831:Animals, Newborn; D001363:Awards and Prizes; D001647:Bile Acids and Salts / Q000378:metabolism; D001648:Bile Canaliculi / Q000187:drug effects; D002478:Cells, Cultured; D002780:Cholestasis, Intrahepatic / Q000209:etiology* / Q000473:pathology; D005217:Fat Emulsions, Intravenous / Q000009:adverse effects / Q000737:chemistry; D005526:Food, Formulated / Q000009:adverse effects*; D013502:General Surgery; D006801:Humans; D007223:Infant; D008099:Liver / Q000166:cytology / Q000378:metabolism; D010288:Parenteral Nutrition / Q000009:adverse effects*; D010840:Phytosterols / Q000008:administration & dosage / Q000009:adverse effects*; D051381:Rats; D012955:Societies, Medical; D013552:Swine; D006113:United Kingdom
D001647:Bile Acids and Salts; D005217:Fat Emulsions, Intravenous; D010840:Phytosterols